Zbinden G, Kleinert R, Rageth B
J Cardiovasc Pharmacol. 1980;2(2):155-64. doi: 10.1097/00005344-198003000-00007.
We explored the usefulness of cardiovascular function studies for the detection and characterization of emetine cardiotoxicity in a subacute toxicity experiment. Rats received 1 mg/kg, s.c., emetine five times weekly for up to 7 weeks. In unanesthetized animals, statistically significant changes of the electrocardiogram (EKG) appeared in the following sequence: prolongation of QRS interval (5th day), flattening of T wave (beginning of 4th week), and prolongation of PR interval (end of 4th week). Terminal cardiovascular studies were conducted under urethane anesthesia. EKG changes were comparable to those recorded in conscious rats, but no decrease in T wave voltage occurred. Blood pressure and heart rate remained unchanged. Cardiac output was decreased after 5 and 7 weeks of treatment, when heart weights were also significantly reduced. The response of cardiac output and mean arterial blood pressure to intravenously injected norepinephrine and epinephrine remained unchanged. Catecholamine-induced arrhythmias occurred less frequently in emetine-treated animals than in controls. No significant structural lesions of the heart muscle were detected by light microscopy. The cardiotoxic effects observed in rats were similar to those reported in humans receiving the usual therapeutic dose of approximately 1 mg/kg/day. We conclude that cardiovascular function studies can make an important contribution to the predictive value of animal toxicity experiments.
在一项亚急性毒性实验中，我们探究了心血管功能研究对于检测吐根碱心脏毒性及描述其特征的有用性。大鼠每周皮下注射1毫克/千克吐根碱，共5次，持续7周。在未麻醉的动物中，心电图（EKG）出现的统计学显著变化按以下顺序：QRS间期延长（第5天）、T波低平（第4周开始）、PR间期延长（第4周结束）。终末期心血管研究在氨基甲酸乙酯麻醉下进行。EKG变化与清醒大鼠记录的变化相当，但T波电压没有降低。血压和心率保持不变。治疗5周和7周后心输出量降低，此时心脏重量也显著减轻。心输出量和平均动脉血压对静脉注射去甲肾上腺素和肾上腺素的反应保持不变。与对照组相比，吐根碱处理的动物中儿茶酚胺诱导的心律失常发生频率较低。光镜检查未发现心肌有明显的结构损伤。在大鼠中观察到的心脏毒性作用与接受约1毫克/千克/天常规治疗剂量的人类报告的作用相似。我们得出结论，心血管功能研究可为动物毒性实验的预测价值做出重要贡献。
